2010 Fiscal Year Final Research Report
Cell migration induced by alternation of extracellular matrix microenvironment
| Project/Area Number |
20590306
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kanazawa University |
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Principal Investigator |
TAKINO Takahisa Kanazawa University, がん研究所, 准教授 (40322119)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 細胞運動 / 浸潤 / ECM / MMP |
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| Research Abstract |
Membrane-type 1 matrix metalloproteinase (MT1-MMP) is essential for tumor invasion and growth. We show here that MT1-MMP induces extracellular signal-regulated kinase (ERK) activation in cancer cells cultured in collagen gel, which is indispensable for their proliferation. Inhibition of MT1-MMP by MMP inhibitor or small interfering RNA suppressed activation of focal adhesion kinase (FAK) and ERK in MT1-MMP-expressing cancer cells, which resulted in up-regulation of p21^<WAF1> and suppression of cell growth in collagen gel. Cell proliferation was also abrogated by the inhibitor against ERK pathway without affecting FAK phosphorylation. MT1-MMP and integrin α_vβ_3 were shown to be involved in c-Src activation, which induced FAK and ERK activation in collagen gel. These MT1-MMP-mediated signal transductions were paxillin dependent, as knockdown of paxillin reduced cell growth and ERK activation, and co-expression of MT1-MMP with paxillin induced ERK activation. The results suggest that MT1-MMP contributes to proliferation of cancer cells in the extracellular matrix by activating ERK through c-Src and paxillin.
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Research Products
(9 results)
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[Journal Article] GI24 enhances tumor invasiveness by regulating cell surface membrane-type 1 matrix metalloproteinase.2010
Author(s)
Sakr, M., Takino, T., Domoto, T., Nakano, H., Wong, R., Sasaki, M., Nakanuma, Y., Sato, H.
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Journal Title
Cancer Science 101
Pages: 2368-2374
Peer Reviewed
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[Journal Article] Activation of matrix metalloproteinase-2 (MMP-2) by membrane type 1 matrix metalloproteinase through an artificial receptor for proMMP-2 generates active MMP-2.2008
Author(s)
Nishida, Y., Miyamori, H., Thompson, E.W., Takino, T., Endo, Y., Sato, H.
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Journal Title
Cancer Research 68
Pages: 9096-9104
Peer Reviewed
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[Journal Article] The scaffold protein c-Jun NH_2-terminal kinase-associated leucine zipper protein regulates cell migration through interaction with the G protein G (alpha 13).2008
Author(s)
Gantulga, D., Tuvshintugs, B., Endo, Y., Takino, T., Sato, H., Murakami, S., Yoshioka, K.
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Journal Title
Journal of Biochemistry 144
Pages: 693-700
Peer Reviewed
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